The goal of this Shared Instrumentation Grant application is to provide photoacoustic imaging to the San Diego research community. Photoacoustic imaging is an optical technique that converts incident excitation light into acoustic waves-it has the contrast and spectral behavior of optics with the spatial/temporal resolution and depth penetration of ultrasound. No similar instrumentation is available in San Diego and upgrading and expanding the ultrasound/photoacoustic imaging capabilities will have a profound impact on many areas of research. More specifically, we propose to upgrade our now obsolete and unsupported VisualSonics 770 with the VisualSonics LAZR Photoacoustic Imaging System, which is a dedicated small animal photoacoustic scanner. The VisualSonics platform is the only photoacoustic scanner that also offers ultrasound imaging for a variety of cancer and cardiac applications, but at the same price point as competing photoacoustic scanners. This allows us to double our user base without requesting additional funds. As a result of this upgrade, we will not only image anatomic structures (tumor size), but will also collect functional information (hemoglobin/deoxyhemoglobin, melanin), physiological information (left ventricle ejection fraction, cardiac strain), and molecular-level information (contrast agents for vascular and extracellular targets). Our user base (15 users; 19 funded grants) has developed a very powerful portfolio of optical imaging probes and adding photoacoustic capabilities to our campus will offer increased spatial and temporal resolution and up to three additional centimeters of depth penetration. This is critical for better image-guided surgical resections and fundamental studies of drug delivery vehicles as well as basic studies into the tumor microenvironment, cancer metastasis, and tumor resection. This system also has a broad portfolio of echocardiography tools to study cardiac repair and remodeling. We believe that this dedicated pre-clinical scanner will ultimately have a powerful impact on human disease including screening, staging, resection guidance, and monitoring response to therapy. UC San Diego offers institutional support, including a dedicated small animal imaging facility based on a recharge model as well as matching funds from the Medical and Engineering Schools. The studies we are proposing-and have already received NIH funding to perform-nicely match the public health goals established by NIH and the UC San Diego. In keeping with the highly interdisciplinary nature of imaging, we describe a broad user base including personnel from Engineering (Drs. Chien, Peter, McCulloch, Jokerst, Christman, etc.), Medicine (Drs. Hall, Vera, Blair, Bouvet, etc.), and Chemistry (Drs. Gianneschi and Tsien). This equipment will not only increase the findings achievable with our existing NIH funding, but will also enable multiple new studies in the fields of cancer, cardiology, inflammation, and neurology.